Regulation of Neuronal Activation by Alpha2A Adrenergic Receptor Agonist

Abstract

Stress factors induce neuronal activation in brain areas that are related to anxiety and fear. High doses of caffeine induce neuronal activation with Ca2+ influx followed by expression of the immediate early gene c-fos. In the present study, we investigated c-Fos protein expression in stress-responsive brain areas induced by caffeine, as well as the role of alpha2A receptor in the regulation of neuronal activation. Immunohistochemical analysis showed that an acute effect of caffeine induced c-Fos protein expression in the hippocampus, the bed nucleus of stria terminalis (BNST), the lateral septum, the basolateral and central amygdala, the paraventricular hypothalamic nucleus (PVN), the locus coeruleus, and the lateral parabrachial nucleus (LPBN). However, c-Fos expression was attenuated after repeated treatment of caffeine, spaced 24 h apart, compared to a single acute effect. Alpha2A receptor activation with the agonist guanfacine attenuated the acute effect of caffeine in terms of c-Fos expression in neurons in the CA1-CA3 areas of hippocampus, the locus coeruleus and the LPBN as compared with effect of caffeine alone, whereas the number of c-Fos expressing neurons increased in the lateral septum, the dorsal BNST, the central amygdala, and the PVN, areas that are densely innervated by noradrenergic neurons. Guanfacine alone induced c-Fos protein expression in neurons in the central amygdala, the dorsal BNST, the PVN, the LPBN, and the caudal nucleus of the solitary tract. Guanfacine alone also induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in neurons expressing c-Fos in the dorsal BNST, the central amygdala, and the LPBN. These results suggest that alpha2A receptor activation modulates synaptic transmission in neuronal circuits that are correlated with stress in vivo.

Effect of Acute Stressor and Serotonin Transporter Genotype on Amygdala First Wave Transcriptome in Mice

“…Increased expression of Ntng2 as observed in our WTs after acute stress in turn therefore might reflect the preparation of the organism to an increased startle response after an acute stressor which resembles a sensitization or increased arousal or fear. A comparable conclusion can be drawn for Adra2a that modulates synaptic transmission via inactivation of adenyl cyclase and decrease of cAMP in response to catecholamines in neuronal circuits that are correlated with stress in vivo [49]. A rapid downregulation as observed in our stressed WTs probably reduces these inhibitory effects, resulting in an enhanced neurotransmitter release and therefore a more vigorous arousal or fear and stress reaction.…”

Variability in nicotine conditioned place preference and stress‐induced reinstatement in mice: Effects of sex, initial chamber preference, and guanfacine

“…The CeA has a well‐established role in stress‐induced behaviors, and the CeL but not the CeM mediates relapse to methamphetamine self‐administration . Guanfacine increased CeL Arc immunoreactivity (Figure C,D), as seen previously, but nicotine‐treated groups showed decreased CeL activity overall. Previous studies have shown enhanced c‐fos immunoreactivity in the CeA after incubation of nicotine self‐administration and after footshock which followed nicotine self‐administration training .…”

Overlapping representation of primary tastes in a defined region of the gustatory cortex

“…Antigen expression, including c-Fos, was assessed using standard IHC procedures, with a rabbit polyclonal anti-c-Fos antibody (sc-52, Santa Cruz Biotechnology); M2-type muscarinic acetylcholine receptors were labeled using a rat monoclonal anti-M2 antibody (MAB 367, EMD Millipore). Primary antibody labeling was visualized with either fluorescent or non-fluorescent secondary antibodies (see our previous papers for detailed methods, (Savchenko and Boughter, 2011;Tokita and Boughter, 2016…”